Safety and Effectiveness of Granulocyte Transfusions in Resolving Infection in People With Neutropenia (The RING Study)

Thousands of people each year are hospitalized for neutropenia, which continues to cause
substantial morbidity and mortality for those affected. Neutropenia is primarily caused by
chemotherapy and various other cancer treatments, such as radiation therapy, biotherapy, and
HSC transplantation. Signs and symptoms of neutropenia may include high fever, chills, sore
throat, and diarrhea. In neutropenia, the number of neutrophils, a type of granulocyte, is
greatly reduced, weakening the body's immune system and increasing the risk of infection.
Therefore, a method to provide adequate numbers of functional granulocytes to people with
neutropenia could be of greatest benefit for recovery. Administration of a combination of
two drugs, granulocyte colony-stimulating factor (G-CSF) and dexamethasone, has been show to
stimulate the body to produce a large number of granulocytes. Granulocyte transfusions
obtained from donors who have received these two drugs may help people with low white blood
cell counts fight infections until their own white blood cell counts recover. However, it is
not clear whether the benefits of granulocyte transfusions outweigh the risks of side
effects. This study will compare the safety and effectiveness of granulocyte transfusions
with standard antimicrobial therapy versus the safety and effectiveness of standard
antimicrobial therapy alone in increasing granulocyte numbers and in improving survival
rates in people with bacterial or fungal infection during neutropenia.

Participation in the research portion of this study will last about 3 months. All
participants who were not previously receiving treatment with standard antimicrobial therapy
will begin therapy immediately upon study entry. Participants will then be assigned randomly
to receive either granulocyte transfusion plus continued antimicrobial therapy or continued
antimicrobial therapy alone. All participants will be monitored for a maximum of 42 days,
during which they will provide information on medical history and ongoing status of
antimicrobial therapy. Daily blood samples to measure white blood cell count will be
obtained from participants until samples show that participants are making their own
granulocytes. Samples will then be collected weekly until Day 42. There may be additional
blood draws depending on the type of infection present in participants.

Granulocyte transfusions will be given daily during the 42-day treatment period, depending
on granulocyte donor availability. Blood counts will be checked immediately before and after
each transfusion to measure granulocyte levels. Transfusions will be stopped if participants
start making their own granulocytes, experience serious side effects, or show a reduction in
infection. At Month 3 after study entry, follow-up information will be collected about all
participants' health status through reviewing their medical records and contacting their
physicians.

Participation for granulocyte donors will last 1 week from the time of donation. Community
donors may provide more than one granulocyte donation, but no more than one donation every 3
days. Frequency of donation from a family member will be according to local blood bank
criteria with approval from a blood bank physician. Both community donors and family donors
are limited to eight donations each year. Twelve hours before each donation, participants
will be injected with Neupogen, which contains G-CSF, and they will take one dose of
dexamethasone by mouth. Participants will then undergo a blood draw, followed by a procedure
using an apheresis machine for granulocyte collection. The procedure will last 3 to 4 hours
and will involve the drawing of blood from each arm, the separation of granulocytes from the
red blood cells and plasma in the machine, and the return of the red blood cells and plasma
to the participants.

Inclusion Criteria:

- Severe neutropenia (Absolute Neutrophil Count < 500/mm^3) due to marrow failure
caused by underlying disease or therapy

- Must have one of the following: fungemia; bacteremia; proven or presumptive invasive
tissue bacterial infection; or proven, probable, or presumptive invasive fungal
infection

Exclusion Criteria:

- Unlikely to survive 5 days

- Evidence that patient will not be neutropenic at least 5 days

- Previously enrolled in this study